The requirement for bone tissue grafting is essential in a wide range of clinical conditions involving surgical reconstruction following trauma or other pathological conditions, particularly in the limbs, spine and skull.
Bone tissue deficits which require bone grafting may arise due to acute traumatic injury to the limbs or following chronic non-union of bone fractures. Additionally, bone deficits may appear following complex joint arthroplasties, e.g. in the hips, knees, elbows or shoulders, or after resection of bone tumours.
Furthermore, bone grafting is essential in surgical fusion of unstable spine and sometimes in reconstructive oral or maxillofacial surgery.
The amount of bone tissue required for grafting, and the destination of the graft material influence the origin of the harvested tissue. For instance, a graft for the purpose of bone induction purposes, i.e. grafting of fresh, autologous cancellous bone, containing cellular, mineral and humoral components, intended to further induce local generation of new bone, is usually taken from a non-involved body site. Bone for conductive-support purposes, involving filling of a large gap, and providing a mechanical support to the treated limb until sufficient new bone is formed would generally require either structural autografts, allografts, or mineral bone matrix substitutes.
A number of disadvantages are associated with both autografts and allografts. Availability of autografts is generally limited, and the harvesting process causes considerable surgical morbidity. The success rate with allografts is limited due to the high risk of “docking site” non-union or rejection of the graft and infection. Furthermore, the osteoinductive and osteoconductive abilities of mineral substitutes are limited to small gaps in the affected bone.
U.S. Pat. No. 6,943,008 discloses a bioreactor for cell culture comprising a chamber for conducting fluids, in which a polyethylene scaffold seeded with cells is placed.
U.S. Pat. No. 5,512,480 discloses a flow-through bioreactor for the retention and culture of cells in perfused media. Neither of these methods is used for generation of bone tissue.
A bioreactor designed by Zetos, Switzerland is used to keep harvested bone samples viable for maintenance of bone tissue ex vivo for research purposes. The device is not disclosed as being suitable for clinical use, or for bone tissue generation.
Yamanouchi K, et al in J. Bone Min. Res. 16(5): 857-867 (2001) describes a method of implantation of autologous osteoblasts seeded ex vivo on collagen sponge for in vivo bone generation. Similarly, Stevens M. M. et al (Proc Natl Acad Sci USA 2005; 102(32)11450-5) describe an animal model of an in vivo bone bioreactor. Neither of these methods is directed to bone tissue generation ex vivo.
U.S. Patent No. 2007/0128174 discloses a method for treating tissue defects in human or animal tissues comprising use of implantable cells. The method may comprise implantation of bone cells and inorganic matrix into a bone gap in order to enhance bone union. The matrices described in the background art are implanted at a target site, wherein the bone cells are released from the matrix, such that the purpose of the matrix is primarily delivery of the cells to the target area and does not generate bone tissue ex vivo.
U.S. Pat. No. 5,103,806 discloses bodily bone mass enhancement by external mechanical vibration. No ex vivo method is taught.